Involvement of Enhanced Glutamate Release in Halogenated volatile Anesthetic-induced Central Nervous System Excitation

增强的谷氨酸释放参与卤化挥发性麻醉剂引起的中枢神经系统兴奋

• 批准号: 06671556
• 负责人: HIROSE Takuji
• 金额: $ 1.34万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671556/
• 关键词: Halogenated Anesthetics; Volatile Anesthetics; Halogenated Ethane; Convulsion; CNS Excitation; Glutamate; Excitatory Amino Acid; Microdialysis; ハロゲン化揮発性麻酔薬; マイクロダイアリシス法; ハロゲン化揮発性吸入麻酔薬

(1)The present experiments aimed to elucidate the mechanisms of excitatory effects of volatile anesthetics and convulsant. In ddN mice, enflurane (2% in air), sevoflurane (2%) or isoflurane (1.2%) induced opisthotonus.In ddY mice, a halogenated ethane, tetrachlorodifluoroethane (CC12FCC12F : DF-112, 2%) induced tonic-clonic convulsion. These CNS excitatory effects were suppressed by pretreatment with an N-methyl-D-aspartate antagonist, MK-801 (0.5mg/kg). Halogenated volatile anesthetics (enflurane, sevoflurane, isoflurane and halothane) increased glutamate release from synaptosomes of the mouse cerebral cortex at concentrations corresponding to those used clinically. By contrast, diethyl ether which has no halogen atoms did not affect glutamate release over a wide range of concentrations. The convulsive gas, DF-112, released glutamate more potently than anesthetics.(2)We have applied brain microdialysis-HPLC procedure to estimate amino acids release in rat hippocampus during the inhalation of halogenated volatile agents. Volatile anesthetics did not affect amino acids levels in dialysates, while volatile convulsant, DF-112 slightly but not significantly increased glutamate level in the dialysate.(3)These data suggest the involment of enhanced glutamate release in the mechanisms of excitatory effects of halogenated volatile anesthetics and convulsants. The CNS excitations must occur when excitatory stimuli resulting from excessive release of excitatory amino acid may overcome postsynaptic inhibition.

（1）本实验旨在阐明挥发性麻醉药和惊厥药兴奋作用的机制。在ddN小鼠中，安氟醚（2%在空气中）、七氟醚（2%）或异氟醚（1.2%）诱导角弓反张，在ddY小鼠中，卤代乙烷、四氯二氟乙烷（CC 12 FCC 12 F：DF-112，2%）诱导强直-阵挛性惊厥。这些中枢神经系统兴奋作用可通过预先使用N-甲基-D-天冬氨酸拮抗剂MK-801（0.5 mg/kg）来抑制。卤代挥发性麻醉剂（恩氟烷、七氟烷、异氟烷和氟烷）在与临床使用的浓度对应的浓度下增加小鼠大脑皮层突触体的谷氨酸释放。相比之下，没有卤素原子的乙醚在很宽的浓度范围内不影响谷氨酸盐的释放。惊厥气体DF-112释放谷氨酸的效力比麻醉剂更强。(2)We应用脑微透析-高效液相色谱法测定了大鼠吸入卤代挥发性药物时海马氨基酸的释放。挥发性麻醉剂不影响透析液中的氨基酸水平，而挥发性惊厥剂DF-112轻微但不显著增加透析液中的谷氨酸水平。（3）提示卤代挥发性麻醉药和惊厥药的兴奋作用机制与谷氨酸释放增加有关。当兴奋性氨基酸的过度释放引起的兴奋性刺激可以克服突触后抑制时，CNS兴奋必然发生。

项目成果

Takuji, Hirose: "Involvement of Enhanced Glutamate Release in Halogenated Volatile Anesthetic-induced Excitation in Mouse Brain" Masui. 46. 338-343 (1997)

Takuji, Hirose：“增强谷氨酸释放参与卤化挥发性麻醉剂引起的小鼠大脑兴奋”Masui。

廣瀬卓治: "ハロゲン化揮発性麻酔薬の中枢興奮作用とグルタミン酸遊離促進作用" 麻酔. 46. 338-343 (1997)

Takuji Hirose：“卤化挥发性麻醉剂的中枢兴奋作用和谷氨酸释放促进作用”麻醉46。338-343（1997）。